Method for evaluating compound amoxicillin powder

Abstract

The invention provides a method for evaluating compound amoxicillin powder, which belongs to the technical field of medicine detection, and comprises the following steps: detecting the content of an effective component of a medicine, and recording the content as the content A of the effective component; enabling the medicine to sequentially pass through the simulated gastric acid environment and the simulated small intestine environment, detecting the active ingredient content of the medicine after passing through the simulated gastric acid environment, recording the active ingredient content as an active ingredient content B, and detecting the active ingredient content of the medicine after passing through the simulated small intestine environment, recording the active ingredient content as an active ingredient content C; and counting the content change of the effective components of the medicine, and evaluating the compound amoxicillin powder. According to the technical scheme provided by the invention, the purposes of simplifying the evaluation method and reducing the cost are achieved.

Description

Technical Field

[0001] This invention relates to the field of drug detection technology, specifically to a method for evaluating compound amoxicillin powder. Background Technology

[0002] With the rapid development of my country's economy, more and more manufacturers have begun producing compound amoxicillin. Currently, over 400 veterinary drug companies nationwide are legally authorized to produce and sell compound amoxicillin. The main components of this drug are amoxicillin and clavulanate potassium. These components are very similar, and may even come from the same supplier. How can these products be compared and selected? Currently, there are many methods for evaluating these drugs. One method is to detect the active ingredient in the drug, such as the Chinese patent CN118409016A, entitled "A High-Performance Liquid Chromatography Detection Method for Compound Amoxicillin and Clavulanic Acid," which discloses a high-performance liquid chromatography method. The mobile phase is methanol-phosphate buffer-water in a ratio of 10:5-15:85-75, with a phosphate buffer pH of 6.0. The method described in this invention provides more accurate results and has a wider range of applicability for the chromatographic column. However, the above detection method cannot reflect the true effect of the drug. Another method is to detect the drug's efficacy, such as drug sensitivity testing (including paper disc method and MIC methods), active ingredient content, water solubility, blood drug concentration, and comparison of clinical application effects. The first few methods are simple and easy to implement, can be completed in the laboratory, and are quick and inexpensive, but the results are quite different from the clinical application effects. The two methods that compare blood drug concentration and clinical application effects are the best, but both of these methods involve a large number of animal experiments, which are very labor-intensive, have long experimental cycles, and are very expensive. Many institutions do not have the conditions to do so.

[0003] In conclusion, there is a need to provide a simple method for evaluating compound amoxicillin powders from different manufacturers. Summary of the Invention

[0004] In view of this, the present invention provides a method for evaluating compound amoxicillin powder, thereby simplifying the evaluation method and reducing costs.

[0005] To achieve the above objectives, the present invention provides a method for evaluating compound amoxicillin powder, comprising the following steps: detecting the content of the active ingredient of the drug, denoted as active ingredient content A; passing the drug sequentially through a simulated gastric acid environment and a simulated small intestinal environment, detecting the content of the active ingredient of the drug after passing through the simulated gastric acid environment, denoted as active ingredient content B, and detecting the content of the active ingredient of the drug after passing through the simulated small intestinal environment, denoted as active ingredient content C; statistically analyzing the changes in the content of the active ingredient of the drug to evaluate the compound amoxicillin powder.

[0006] Optionally, the simulated gastric acid environment includes a pH of 1.5 to 2.5.

[0007] Optionally, a hydrochloric acid solution of 0.01~0.015 mol / L can be used to simulate the gastric acid environment.

[0008] Optionally, the simulated small intestinal environment includes a pH of 6-7.

[0009] Optionally, a 0.8–1.2 mol / L NaHCO3 solution can be used to simulate the small intestinal environment.

[0010] Optional, the following steps may be included: S1. Take the sample to be evaluated, dissolve it in purified water and make up to volume. The sample solution is named SA. The effective components of SA are detected and recorded as the effective component content A. S2. Take the sample to be evaluated, dissolve it in hydrochloric acid solution and dilute it to a fixed volume. After mixing, measure the pH value of the solution and record it. Heat the SA sample solution in a water bath. At this time, the sample solution is named SB, and the content of the effective ingredient is recorded as the content of the effective ingredient B. S3. Add the SB sample solution to NaHCO3 solution, mix well, measure the pH value of the solution and record it; heat the SB sample solution in a water bath, at this time the sample solution is named SC, and the content of the effective ingredient is recorded as the content of the effective ingredient C. S4. Statistically analyze the contents of effective ingredients A, B, and C, and assess their changes.

[0011] Optionally, the sample to be evaluated is 0.2g, dissolved in purified water and diluted to 100ml; the sample to be evaluated is 0.2g, dissolved in hydrochloric acid solution and diluted to 100ml; 1.0ml of NaHCO3 solution is added to the SB sample solution.

[0012] Optionally, the SA sample solution can be heated in a water bath at 37°C for 30-60 minutes; the SB sample solution can be heated in a water bath at 37°C for 10-45 minutes.

[0013] Optionally, the method for detecting the content of the active ingredient is high performance liquid chromatography, with the following chromatographic conditions: stationary phase: octadecylsilane-bonded silica gel; mobile phase: methanol-phosphate buffer-water in a ratio of 10:1:89; and detection wavelength: 215 nm.

[0014] Optionally, the sample may be processed before detecting the content of the active ingredient. The processing includes the following steps: filtering the sample through a 0.22 μm filter membrane, discarding the initial filtrate, accurately measuring 10 μl of the subsequent filtrate, and injecting it into the liquid chromatograph.

[0015] The above-described technical solution of the present invention has at least the following beneficial effects: The technical solution provided by this invention evaluates the efficacy of compound amoxicillin powder by simulating the process of drugs passing through the digestive tract. The operation is simple and easy. After ingestion or drinking, the drug enters the digestive tract and undergoes a series of changes. Among these, the most significant impacts are: first, encountering stomach acid, at which point the pH value rapidly drops to around 1-4; and after a period of time, encountering substances such as bicarbonate, causing the pH value to rise dramatically to around 7. These drastic environmental changes greatly affect compound amoxicillin powder. The purpose of this invention is to simulate these changes in the laboratory and evaluate the drug by detecting changes in the content of the tested drug. This method is simple, low-cost, and highly discriminative, effectively distinguishing and evaluating products from different manufacturers. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.

[0017] This invention provides a method for evaluating compound amoxicillin powder, comprising the following steps: detecting the content of the active ingredient in the drug, denoted as active ingredient content A; sequentially passing the drug through a simulated gastric acid environment and a simulated small intestinal environment, detecting the content of the active ingredient in the drug after passing through the simulated gastric acid environment, denoted as active ingredient content B, and detecting the content of the active ingredient in the drug after passing through the simulated small intestinal environment, denoted as active ingredient content C; statistically analyzing the changes in the content of the active ingredient in the drug to evaluate the compound amoxicillin powder.

[0018] Example 1 This invention provides a method for evaluating compound amoxicillin powder, comprising the following steps: Seven compound amoxicillin products were randomly selected from the market. (1) Take the samples to be evaluated and number them as S1, S2, S3, S4, S5, S6 and S7 respectively. Take 0.2g from each of S1-S7 into a 100ml volumetric flask, dissolve it with purified water and make up to the mark, shake well. Name the 100ml sample solutions as S1-A, S2-A, S3-A, S4-A, S5-A, S6-A and S7-A respectively.

[0019] (2) Take the samples to be evaluated and number them as S1, S2, S3, S4, S5, S6 and S7 respectively. Take 0.2g from each of S1-S7, dissolve them in 0.01mol / L hydrochloric acid solution and make up to 100ml. Measure the pH value and record it as pH-S1-B, pH-S2-B, pH-S3-B, pH-S4-B, pH-S5-B, pH-S6-B and pH-S7-B.

[0020] (3) The sample solution dissolved in 0.01 mol / L hydrochloric acid solution in step (2) is treated in a water bath at 37°C for 30-60 min. The sample solutions are named S1-B, S2-B, S3-B, S4-B, S5-B, S6-B and S7-B respectively.

[0021] (4) Add 1.0 ml of 1 mol / L NaHCO3 solution to the SB sample solution treated with the above 0.01 mol / L hydrochloric acid solution, shake well, measure the pH value and record it as pH-S1-C, pH-S2-C, pH-S3-C, pH-S4-C, pH-S5-C, pH-S6-C and pH-S7-C. Treat the sample solution in a 37℃ water bath for 10-45 min, and name the sample solution as S1-C, S2-C, S3-C, S4-C, S5-C, S6-C and S7-C.

[0022] (5) Filter the SA, SB, and SC series sample solutions through a 0.22 μm filter membrane, discard the initial filtrate, accurately measure 10 μL of the subsequent filtrate, inject it into the liquid chromatograph, and record the chromatogram; separately take appropriate amounts of amoxicillin reference standard and clavulanic acid reference standard, accurately weigh them, add water to dissolve them, and quantitatively dilute them to prepare a solution containing 0.2 mg of amoxicillin and 50 μg of clavulanic acid per 1 ml, and determine them in the same way. Calculate the content of amoxicillin and potassium clavulanate by peak area according to the external standard method.

[0023] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the stationary phase; methanol-phosphate buffer (pH 6.0)-water (10:1:89) as the mobile phase; and a detection wavelength of 215 nm. The theoretical plate number, calculated based on the amoxicillin and clavulanic acid peaks respectively, was not less than 1500. The resolution between the amoxicillin and clavulanic acid peaks should meet the requirements.

[0024] The pH results are shown in Table 1, and the content of active ingredients is shown in Table 2.

[0025] Table 1. Statistical results of pH

[0026] Table 2 Content of Active Ingredients

[0027] Table 2 shows that after compound amoxicillin powder was treated with 0.01 mol / L (pH 2.0) hydrochloric acid for 30-60 min, followed by environmental treatment at pH 6.5 for 10-45 min, the content of the active ingredient, potassium clavulanate, was severely damaged, leading to a decrease in content. The degree of content reduction varied significantly among different manufacturers. The lowest degradation rate was 67.1%, and the highest was 94.8%. Amoxicillin, after undergoing the same treatment, showed some changes, with content variations ranging from 3.2% to 7.3%, and the differences between manufacturers were smaller than those for potassium clavulanate.

[0028] The above results indicate that the content of active ingredients in compound amoxicillin powder differs significantly after treatment in a simulated gastrointestinal environment. This method can rapidly and effectively reflect changes in the active ingredients in compound amoxicillin powder and can be used for the evaluation of this drug.

[0029] Example 2 Compared to Example 1, pH testing can be omitted to simplify the testing steps.

[0030] Example 3 Compared to Example 1, the sodium bicarbonate treatment can be omitted, which can save more time.

[0031] Example 4 Compared to Example 1, amoxicillin can be omitted, and only potassium clavulanate can be detected.

[0032] The drugs to be tested and evaluated in the technical solution of this invention are not limited to compound amoxicillin powder. This method can also be applied to the evaluation of other oral drugs after being fine-tuned by professionals.

[0033] The above are preferred embodiments of the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for evaluating compound amoxicillin powder, characterized in that, Includes the following steps: The content of the active ingredient in the drug is measured and recorded as active ingredient content A. The drug is then passed through a simulated gastric acid environment and a simulated small intestinal environment. After passing through the simulated gastric acid environment, the content of the active ingredient in the drug is measured and recorded as active ingredient content B. After passing through the simulated small intestinal environment, the content of the active ingredient in the drug is measured and recorded as active ingredient content C. The changes in the content of the active ingredient in the drug are statistically analyzed to evaluate the compound amoxicillin powder.

2. The method for evaluating compound amoxicillin powder according to claim 1, characterized in that, The simulated gastric acid environment includes a pH of 1.5 to 2.

5.

3. The method for evaluating compound amoxicillin powder according to claim 1, characterized in that, A hydrochloric acid solution of 0.01~0.015 mol / L was used to simulate the gastric acid environment.

4. The method for evaluating compound amoxicillin powder according to claim 1, characterized in that, The simulated small intestinal environment includes a pH of 6-7.

5. The method for evaluating compound amoxicillin powder according to claim 1, characterized in that, The small intestinal environment was simulated using 0.8–1.2 mol / L NaHCO3 solution.

6. The method for evaluating compound amoxicillin powder according to claim 1, characterized in that, Includes the following steps: S1. Take the sample to be evaluated, dissolve it in purified water and make up to volume. The sample solution is named SA. The effective components of SA are detected and recorded as the content of effective components A. S2. Take the sample to be evaluated, dissolve and dilute it with hydrochloric acid solution, mix well, measure the pH value of the solution and record it; heat the SA sample solution in a water bath, and name the sample solution SB at this time, and record the content of the effective ingredient as the content of the effective ingredient B. S3. Add the SB sample solution to NaHCO3 solution, mix well, measure the pH value of the solution, and record it; heat the SB sample solution in a water bath, and name the sample solution SC at this time, and record the effective ingredient content as the effective ingredient content C. S4. Statistically analyze the contents of effective ingredients A, B, and C, and assess their changes.

7. The method for evaluating compound amoxicillin powder according to claim 6, characterized in that, The sample to be evaluated was 0.2g, dissolved in purified water and diluted to 100ml; the sample to be evaluated was 0.2g, dissolved in hydrochloric acid solution and diluted to 100ml; 1.0ml of NaHCO3 solution was added to the SB sample solution.

8. The method for evaluating compound amoxicillin powder according to claim 6, characterized in that, Heat the SA sample solution in a 37°C water bath for 30-60 minutes; heat the SB sample solution in a 37°C water bath for 10-45 minutes.

9. The method for evaluating compound amoxicillin powder according to claim 6, characterized in that, The method for detecting the content of the active ingredient is high performance liquid chromatography (HPLC). The chromatographic conditions are: stationary phase: octadecylsilane-bonded silica gel; mobile phase: methanol-phosphate buffer-water in a ratio of 10:1:89; and detection wavelength: 215 nm.

10. The method for evaluating compound amoxicillin powder according to claim 6, characterized in that, Before detecting the content of active ingredients, the sample is processed, which includes the following steps: filter the sample through a 0.22 μm filter membrane, discard the initial filtrate, accurately measure 10 μl of the subsequent filtrate, and inject it into the liquid chromatograph.

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